权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

TCD with Transfusions Changing to Hydroxyurea - SDMC

TCD 输血改为羟基脲 - SDMC

基本信息

批准号：
7920181
负责人：
BARRY R DAVIS
金额：
$ 72.61万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-21 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7920181
关键词：
Academic Medical Centers Address Adult Adverse effects Adverse event Alternative Therapies Annual Reports Archives Arrhythmia Autoantibodies Blood Transfusion Case Report Form Cerebrovascular Disorders Cerebrum Chelation Therapy Child Chronic Clinical Clinical Investigator Clinical Research Clinical Trials Collaborations Communication Communities Companions Computers Coupled Data Data Coordinating Center Data Set Databases Deferoxamine Deferoxamine Methanesulfonate Diabetes Mellitus Doppler Ultrasound Effectiveness Electronics Enrollment Ensure Erythrocyte Transfusion Erythrocytes Evaluation Event Excision Frequencies Funding Goals Grant Growth and Development function Incidence Infectious Agent Internal carotid artery structure Iron Iron Chelation Iron Overload Isoantibodies Laboratories Lead Leadership Literature Liver Cirrhosis Liver Fibrosis Maintenance Manuals Masks Measurement Measures Medical Methods Monitor Morbidity - disease rate National Heart, Lung, and Blood Institute Neurocognitive Deficit Neurologic Organ Pain Paper Patients Phase Play Preparation Primary Prevention Process Prophylactic treatment Protocols documentation Publications Quality of life Randomized Randomized Clinical Trials Reporting Research Institute Research Personnel Risk Risk Factors Role Safety Saint Jude Children&apos s Research Hospital Sample Size Screening procedure Secure Serious Adverse Event Services Sickle Cell Sickle Cell Anemia Site Site Visit Source South Carolina Specimen Statistical Methods Stroke Stroke prevention Sudden Death System Testing Time Training Transfusion Venous blood sampling abstracting acute chest syndrome arm base clinical efficacy clinical research site data management design electronic data experience high risk hydroxyurea improved intracranial artery iron chelation therapy meetings middle cerebral artery mortality motor deficit non-compliance operation patient registry prevent protocol development rho software systems statistics success web site

项目摘要

DESCRIPTION (provided by applicant): Stroke occurs in 5-10% of children with SCA, and is a devastating clinical event that results in severe motor and neurocognitive deficits. To help prevent an initial (primary) stroke, young patients with SCA can receive periodic TCD screening to identify children with elevated arterial velocities in the cerebral vasculature, which portends increased primary stroke risk. For children with time-averaged maximum velocities (TAMV) in the middle cerebral artery (MCA) or internal carotid artery (ICA) elevated to the "abnormal" range (=200cm/sec), chronic erythrocyte transfusions significantly lower the risk of primary stroke. In this setting, transfusions can prevent first stroke but have serious side-effects limiting their long-term utility. Transfusions transmit infectious agents, lead to erythrocyte alloantibody or autoantibody formation, and result in iron overload. Transfusion acquired iron overload is recognized as a source of morbidity and mortality for young patients with SCA receiving transfusions for prevention of primary stroke. Chelation therapy can help prevent iron accumulation, but is difficult to tolerate and non-compliance is common. An alternative to transfusion prophylaxis for primary stroke prevention is clearly needed, especially one that also provides an opportunity to address the issue of transfusion acquired iron overload. We propose a Phase III randomized clinical trial for children with sickle cell anemia (SCA) and abnormal Transcranial Doppler (TCD) velocities, termed the "TCD With Transfusions Changing to Hydroxyurea" (TWiTCH) trial. Our hypothesis is that hydroxyurea can maintain a similar TCD velocity as erythrocyte transfusions, and therefore serve as non-inferior therapy, for primary stroke prevention in high risk children with SCA. The primary aim of the TWiTCH trial is to compare standard therapy (transfusions) to alternative therapy (hydroxyurea) for maintenance of TCD velocities in children with SCA on chronic transfusions for abnormal TCD velocities. Additional aims of TWiTCH include comparison of standard to alternative therapy for incidence of primary stroke, determination of the frequency of non-stroke neurological events and other sickle cell-related events, management of iron overload, assessment of growth and development, recording of adverse events, and measurement of quality of life. (End of Abstract)

描述（由申请人提供）： 5-10% 的 SCA 儿童会发生中风，这是一种毁灭性的临床事件，会导致严重的运动和神经认知缺陷。为了帮助预防初次（原发性）中风，患有 SCA 的年轻患者可以接受定期 TCD 筛查，以识别脑血管系统中动脉速度升高的儿童，这预示着原发性中风风险增加。对于大脑中动脉（MCA）或颈内动脉（ICA）的时间平均最大速度（TAMV）升高至“异常”范围（=200厘米/秒）的儿童，慢性红细胞输注可显着降低原发性中风的风险。在这种情况下，输血可以预防首次中风，但会产生严重的副作用，限制了其长期使用。输血传播感染因子，导致红细胞同种抗体或自身抗体形成，并导致铁超负荷。输血获得性铁超负荷被认为是接受输血预防原发性卒中的年轻 SCA 患者发病和死亡的一个根源。螯合疗法有助于防止铁蓄积，但难以耐受且不依从性也很常见。显然需要一种替代输血预防的方法来预防中风，尤其是一种可以解决输血获得性铁超负荷问题的方法。我们提议针对镰状细胞性贫血 (SCA) 和经颅多普勒 (TCD) 速度异常的儿童进行 III 期随机临床试验，称为“TCD 输血改为羟基脲”(TWiTCH) 试验。我们的假设是，羟基脲可以维持与红细胞输注相似的 TCD 速度，因此对于患有 SCA 的高危儿童的初级卒中预防来说，可以作为非劣效疗法。 TWiTCH 试验的主要目的是比较标准疗法（输血）与替代疗法（羟基脲）对于因 TCD 速度异常而长期输血的 SCA 儿童维持 TCD 速度的效果。 TWiTCH 的其他目标包括比较原发性中风发生率的标准疗法与替代疗法、确定非中风神经系统事件和其他镰状细胞相关事件的频率、铁过载的管理、生长和发育的评估、不良事件的记录以及生活质量的测量。（摘要完）